Cytokines are soluble proteinaceous substances produced by a wide variety of haemopoietic and non-haemopoietic cell types, and are critical to the functioning of both innate and adaptive immune responses. Apart from their role in the development and functioning of the immune system, and their aberrant modes of secretion in a variety of immunological, inflammatory and infectious diseases, cytokines are also involved in several developmental processes during human embryogenesis. Thus, cytokines often act locally, but can also have effects on the whole body. For example, cytokines are able to interact directly with the evolving biology of an injury, trauma, or disease.
Thus, compounds having cytokine mediating activity have the potential to be used inter alia in the treatment of stroke, AIDS, multiple sclerosis, infection, spinal cord injuries, musculo-skeletal pain, and injuries to the skin. Currently, compounds having cytokine mediating activity have application in rheumatoid arthritis, cancer, stroke, spinal cord injuries, autoimmune diseases, pain, and inflammation.
Currently, there are about 20,000 products sold worldwide for the treatment of pain and inflammation that are based on aspirin or one or its derivatives. As a result these products tend to work in a similar manner and target pain and inflammation in a similar way. All these drugs function by inhibiting prostaglandins, whose roles include the protection of the gastrointestinal lining. In 1998, 16,000 people in the USA alone died from gastrointestinal complications linked to anti-arthritis drugs.
In addition, pain and inflammation involve more than just prostaglandin and thromboxane. In fact, an average painful musculo-skeletal event will involve around 20 cytokines and endotoxins, many of which play a critical role in determining the severity of the body's response to an injury. Three of the most important cytokines in this process are TNF-alpha, IL-1beta, and IL-6.
Therefore there is a continued need for agents having cytokine mediating activity, as these may be useful in the treatment of numerous diseases and disorders, pain, and inflammation.